Publication Date:
2012-11-07
Description:
By characterizing the geographic and functional spectrum of human genetic variation, the 1000 Genomes Project aims to build a resource to help to understand the genetic contribution to disease. Here we describe the genomes of 1,092 individuals from 14 populations, constructed using a combination of low-coverage whole-genome and exome sequencing. By developing methods to integrate information across several algorithms and diverse data sources, we provide a validated haplotype map of 38 million single nucleotide polymorphisms, 1.4 million short insertions and deletions, and more than 14,000 larger deletions. We show that individuals from different populations carry different profiles of rare and common variants, and that low-frequency variants show substantial geographic differentiation, which is further increased by the action of purifying selection. We show that evolutionary conservation and coding consequence are key determinants of the strength of purifying selection, that rare-variant load varies substantially across biological pathways, and that each individual contains hundreds of rare non-coding variants at conserved sites, such as motif-disrupting changes in transcription-factor-binding sites. This resource, which captures up to 98% of accessible single nucleotide polymorphisms at a frequency of 1% in related populations, enables analysis of common and low-frequency variants in individuals from diverse, including admixed, populations.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3498066/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3498066/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉1000 Genomes Project Consortium -- Abecasis, Goncalo R -- Auton, Adam -- Brooks, Lisa D -- DePristo, Mark A -- Durbin, Richard M -- Handsaker, Robert E -- Kang, Hyun Min -- Marth, Gabor T -- McVean, Gil A -- 085532/Wellcome Trust/United Kingdom -- 086084/Wellcome Trust/United Kingdom -- 090532/Wellcome Trust/United Kingdom -- 095908/Wellcome Trust/United Kingdom -- AI077439/AI/NIAID NIH HHS/ -- AI2009061/AI/NIAID NIH HHS/ -- BB/I021213/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- BB/I02593X/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- DP2OD6514/OD/NIH HHS/ -- ES015794/ES/NIEHS NIH HHS/ -- G0701805/Medical Research Council/United Kingdom -- G0801823/Medical Research Council/United Kingdom -- G0900747/Medical Research Council/United Kingdom -- G0900747(91070)/Medical Research Council/United Kingdom -- G12 MD007579/MD/NIMHD NIH HHS/ -- G12 RR003050/RR/NCRR NIH HHS/ -- HHSN268201100040C/PHS HHS/ -- HL078885/HL/NHLBI NIH HHS/ -- P01 HG004120/HG/NHGRI NIH HHS/ -- P01HG4120/HG/NHGRI NIH HHS/ -- P20 MD006899/MD/NIMHD NIH HHS/ -- P30 AG038072/AG/NIA NIH HHS/ -- P41HG2371/HG/NHGRI NIH HHS/ -- P41HG4221/HG/NHGRI NIH HHS/ -- R01 CA166661/CA/NCI NIH HHS/ -- R01 HG002898/HG/NHGRI NIH HHS/ -- R01 HG004960/HG/NHGRI NIH HHS/ -- R01 HG007022/HG/NHGRI NIH HHS/ -- R01CA166661/CA/NCI NIH HHS/ -- R01GM59290/GM/NIGMS NIH HHS/ -- R01HG2898/HG/NHGRI NIH HHS/ -- R01HG3698/HG/NHGRI NIH HHS/ -- R01HG4719/HG/NHGRI NIH HHS/ -- R01HG4960/HG/NHGRI NIH HHS/ -- R01HG5701/HG/NHGRI NIH HHS/ -- R01HL95045/HL/NHLBI NIH HHS/ -- R01MH84698/MH/NIMH NIH HHS/ -- RC2HG5552/HG/NHGRI NIH HHS/ -- RC2HG5581/HG/NHGRI NIH HHS/ -- RC2HL102925/HL/NHLBI NIH HHS/ -- RG/09/012/28096/British Heart Foundation/United Kingdom -- RG/09/12/28096/British Heart Foundation/United Kingdom -- T15 LM007056/LM/NLM NIH HHS/ -- T15LM7033/LM/NLM NIH HHS/ -- T32GM7748/GM/NIGMS NIH HHS/ -- T32GM8283/GM/NIGMS NIH HHS/ -- T32HL94284/HL/NHLBI NIH HHS/ -- U01 HG005728/HG/NHGRI NIH HHS/ -- U01 HG006513/HG/NHGRI NIH HHS/ -- U01HG5208/HG/NHGRI NIH HHS/ -- U01HG5209/HG/NHGRI NIH HHS/ -- U01HG5211/HG/NHGRI NIH HHS/ -- U01HG5214/HG/NHGRI NIH HHS/ -- U01HG5715/HG/NHGRI NIH HHS/ -- U01HG5725/HG/NHGRI NIH HHS/ -- U01HG5728/HG/NHGRI NIH HHS/ -- U01HG6513/HG/NHGRI NIH HHS/ -- U01HG6569/HG/NHGRI NIH HHS/ -- U41HG4568/HG/NHGRI NIH HHS/ -- U54 HG003273/HG/NHGRI NIH HHS/ -- U54HG3067/HG/NHGRI NIH HHS/ -- U54HG3079/HG/NHGRI NIH HHS/ -- U54HG3273/HG/NHGRI NIH HHS/ -- UL1 TR000124/TR/NCATS NIH HHS/ -- UL1RR024131/RR/NCRR NIH HHS/ -- WT085475/Z/08/Z/Wellcome Trust/United Kingdom -- WT085532AIA/Wellcome Trust/United Kingdom -- WT086084/Z/08/Z/Wellcome Trust/United Kingdom -- WT089250/Z/09/Z/Wellcome Trust/United Kingdom -- WT090532/Z/09/Z/Wellcome Trust/United Kingdom -- WT095552/Z/11/Z/Wellcome Trust/United Kingdom -- WT098051/Wellcome Trust/United Kingdom -- Howard Hughes Medical Institute/ -- England -- Nature. 2012 Nov 1;491(7422):56-65. doi: 10.1038/nature11632.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23128226" target="_blank"〉PubMed〈/a〉
Keywords:
Alleles
;
Binding Sites/genetics
;
Conserved Sequence/genetics
;
Continental Population Groups/genetics
;
Evolution, Molecular
;
Genetic Variation/*genetics
;
Genetics, Medical
;
*Genetics, Population
;
Genome, Human/*genetics
;
Genome-Wide Association Study
;
*Genomics
;
Haplotypes/genetics
;
Humans
;
Nucleotide Motifs
;
Polymorphism, Single Nucleotide/genetics
;
Sequence Deletion/genetics
;
Transcription Factors/metabolism
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
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